Role of hypoxia-inducible factor-1α, carbonic anhydrase-IX, glucose transporter-1 and vascular endothelial growth factor associated with lymph node metastasis and recurrence in patients with locally advanced cervical cancer

The aim of the present study was to determine whether the expression of hypoxia-inducible factor-la (HIF-1 alpha), carbonic anhydrase-IX (CA-IX), glucose transporter-1 (GLUT-1) or vascular endothelial growth factor (VEGF) was associated with the clinicopathological characteristics, lymph node metastasis or progression-free survival of patients with cervical cancer. Tumor tissue samples were obtained from 54 cervical cancer patients who had undergone radical hysterectomy. The expression of HIF-1 alpha, CA-IX, GLUT-1 and VEGF was analyzed by immunohistochemical staining. Of the 54 cases, 28 were positive for HIF-1 alpha, 35 for CA-IX, 40 for GLUT-1 and 23 for VEGF. It was revealed that HIF-1 alpha expression was correlated with tumor stage and histology, CA-IX expression with tumor stage, tumor size, lymph node metastasis and lymph-vascular space involvement, GLUT-1 expression with tumor stage and lymph-vascular space involvement, and VEGF expression with microvessel density. The multivariate regression analysis indicated that CA-IX expression and lymph-vascular space involvement were independent variables associated with lymph node metastasis. Progression-free survival was shorter for patients who were positive for CA-IX or VEGF expression than for those who were negative for CA-IX or VEGF expression. The progression-free survival of patients treated with radiotherapy or chemo-radiotherapy following radical hysterectomy was also shorter for patients with positive CA-IX expression. These findings suggest that CA-IX expression is a possible risk factor for lymph node metastasis and disease recurrence in locally advanced cervical cancer patients.